Efficient Oxidative Dearomatisations of Substituted Phenols Using Hypervalent Iodine (III) Reagents and Antiprotozoal Evaluation of the Resulting Cyclohexadienones against <i>T. b. rhodesiense</i> and <i>P. falciparum</i> Strain NF54

Quinones and quinols are secondary metabolites of higher plants that are associated with many biological activities. The oxidative dearomatization of phenols induced by hypervalent iodine(III) reagents has proven to be a very useful synthetic approach for the preparation of these compounds, which ar...

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Bibliographic Details
Main Authors: Nina Scheiber, Gregor Blaser, Eva-Maria Pferschy-Wenzig, Marcel Kaiser, Pascal Mäser, Armin Presser
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/19/6559
Description
Summary:Quinones and quinols are secondary metabolites of higher plants that are associated with many biological activities. The oxidative dearomatization of phenols induced by hypervalent iodine(III) reagents has proven to be a very useful synthetic approach for the preparation of these compounds, which are also widely used in organic synthesis and medicinal chemistry. Starting from several substituted phenols and naphthols, a series of cyclohexadienone and naphthoquinone derivatives were synthesized using different hypervalent iodine(III) reagents and evaluated for their in vitro antiprotozoal activity. Antiprotozoal activity was assessed against <i>Plasmodium falciparum</i> NF54 and <i>Trypanosoma brucei rhodesiense</i> STIB900. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. We found that benzyl naphthoquinone <b>5c</b> was the most active and selective molecule against <i>T. brucei rhodesiense</i> (IC<sub>50</sub> = 0.08 μM, SI = 275). Furthermore, the antiprotozoal assays revealed no specific effects. In addition, some key physicochemical parameters of the synthesised compounds were calculated.
ISSN:1420-3049